Disease In HIV-infected Patients Research Articles

Response to Mallet et al., ‘Nodular regenerative hyperplasia is a new cause of chronic liver disease in HIV-infected patients’

Response to Mallet et al., ‘Nodular regenerative hyperplasia is a new cause of chronic liver disease in HIV-infected patients’

Nodular regenerative hyperplasia: a new serious antiretroviral drugs side effect?

In a recent article, Mallet and colleagues [1] reported a series of eight cases of nodular regenerative hyperplasia (NRH) of the liver as a new cause of chronic liver disease in HIV-infected patients. NRH is characterized ‘by the presence of diffuse rather small regenerative nodules in the absence of significant fibrosis’. All patients were treated with HAART and all received didanosine included in one of several lines of antiretroviral drugs they had before the diagnosis of NRH. The authors speculate that a prothrombotic state enhanced by both HIV infection and didanosine toxicity may result in intrahepatic thrombosis leading to NRH. The prevalence of such cases could have been underestimated and we think is of interest to report similar cases. We would therefore like briefly to report a case diagnosed in Martinique, where we are presently following 700 HIV-infected patients. A 49-year-old woman was diagnosed with HIV in November 1996. In her records she reported a liver fracture associated with multiple trauma after a motorcycle crash in 1976. The liver was sutured and recovery was good. No analgesics were taken between 1976 and 1996. Oral contraceptives were the only drugs taken during that period (less than 24 months' cumulative exposure). At HIV diagnosis, the viral load was 36 000 copies/ml and the CD4 cell count was 414 cells/μl. In December 1996, a first line of HAART was initiated including didanosine, zidovudine and nevirapine and was stopped in July 2005 after 111 months for possible viramune hepatic toxicity. One year after the initiation of HAART non-icteric cholestasis had developed, with the gamma glutamyl transferase level reaching 10 times the upper limit of normal (ULN) and alkaline phosphatases reaching five times the ULN. Three years later there was a moderate cytolytic hepatitis with aspartate aminotransferase reaching 2.5 × ULN and alanine aminotransferase 1.5 × ULN, whereas the prothrombin time decreased to 60%, factor V to 65%, and thrombocytopenia was approximately 70 000 copies/m3, suggesting mild liver failure. In 2006, 5 years after the initiation of HAART, the patient presented with enlarged liver and spleen, portal hypertension with ascites and grade 1 gastroesophageal varices that improved with treatment by aldactone started in October 2005. She complained of iterative acute splenic pain. There was neither a history of alcohol intake nor toxic exposure. Laboratory work-up excluded shistosomiasis, viral hepatitis, autoimmune processes, haemochromatosis, alpha-1 antitrypsin deficiency and Wilson's disease. In April 2004 a liver biopsy had ruled out a specific parasitosis, mycosis or tumour and showed nodules of regenerating hepatocytes. Nodules were separated from the normal area by a dense net of reticuline fibres, and inside were rows of two to three enlarged hepatocytes (see Fig. 1) and vascular abnormalities with peliosis. There was no fibrosis. Although Bartonella serology was negative, the patient received clarithromycin without improvement.Fig. 1: Liver biopsy of the patient performed in April 2004, showing nodules of regenerating hepatocytes. Nodules are separated from the normal area by a dense net of reticuline fibres, and inside are rows of two to three enlarged hepatocytes and vascular abnormalities with peliosis. There is no fibrosisThe HIV-RNA level had been undetectable (below 200 copies/ml) under the first line,whereas theCD4 cell count slowly dropped to 176 cells/μl. After the first line was stopped, cotrimoxazole prophylaxis was started in June 2005, but no antiretroviral treatment was given during the 8 months after HAART ended. A new line of treatment was started in March 2006 with lopinavir, tenofovir and emtricitabine. Under this treatment, the HIV-RNA level is presently below 40 copies/ml and the CD4 cell count is 220 cells/μl. A retrospective diagnosis of NRH was made based on criteria defined by Mallet et al.[1]: (i) cryptogenic liver disease with abnormal liver function for more than 6 months, signs of portal hypertension and ultrasonographic liver dysmorphia; (ii) micronodulation with an alteration of thickened and compressed liver cells or suspected with the association of sinusoidal dilatation and clinical signs of portal hypertension. Finally, NHR is a classic evolution of peliosis. Our case is very similar to those reported by Mallet et al.[1] and emphasizes the seriousness of this complication: the risk of variceal haemorrhage, indication for some patients of transplantation (three out of eight of the cases reported by Mallet et al. [1]). Only HIV infection and HAART have been identified as potential co-factors. Nevirapine toxicity is well known, has not been specifically incriminated in NRH pathogenesis, but was also taken by our patient as well as by eight patients reported by Mallet et al. [1]. We agree with the authors that special attention should be paid to any hepatic dysfunction, however minor, under HAART that cannot be related to an identifiable cause.

HIV-1 and HIV-Associated Nephropathy 25 Years Later

Twenty-five years after the first published description of AIDS, HIV-associated nephropathy (HIVAN) remains an important cause of kidney disease in HIV-infected patients. The pathogenesis of HIVAN involves direct HIV infection of the kidney, with both viral and host genetic factors playing an important role. The widespread use of antiretroviral therapy has influenced the epidemiology of HIV-related kidney disease, and the nephrology community should support efforts to improve access to therapy and limit HIV transmission in susceptible minority populations. This article reviews the history of HIV and HIVAN, focusing on advances in the understanding of pathogenesis, epidemiology, and treatment.

Thoracic Radiographic and CT Findings of Multicentric Castleman Disease in HIV-infected Patients

Multicentric HIV-related Castleman disease (MCD) is a rare and severe disorder of lymphoid tissue inducing high-grade fever, hepatosplenomegaly, and diffuse peripheral lymphadenopathy. During clinical exacerbations, bilateral interstitial pneumonia may occur. In this pictorial essay, we describe different thoracic imaging of MCD, with particular emphasis on computed tomography findings, in 13 HIV-infected patients with histologically proved MCD.

P653 Mycobacterium tuberculosis disease in HIV-infected patients in HAART era

P653 Mycobacterium tuberculosis disease in HIV-infected patients in HAART era

The nephrologist in the HAART era

The nephrologist in the HAART era

Considerations on the increase in blood pressure among antiretroviral-naive patients starting HAART

Considerations on the increase in blood pressure among antiretroviral-naive patients starting HAART

Nodular regenerative hyperplasia is a new cause of chronic liver disease in HIV-infected patients

To describe and explain the syndrome of HIV-associated cryptogenic liver disease in eight consecutive patients suffering from portal hypertension. The study was undertaken at a liver disease centre in Paris and involved eight of 97 consecutive HIV-infected patients presenting abnormal liver function tests and/or symptomatic portal hypertension of unknown origin. Serology, pathology, and liver function tests were performed. A clear nodular architecture corresponding to nodular regenerative hyperplasia was observed in seven patients and suggested in one, based on the presence of sinusoidal dilatation in a clinical context of portal hypertension, without overt liver disease. Nodular regenerative hyperplasia appears to be a new cause of portal hypertension in HIV-infected patients. This syndrome can be of critical importance as patients can be exposed to the significant complications of portal hypertension and to refractory ascites which may require liver transplantation.

Fatal infection due to larval cysts of cestodes (neurocysticercosis and hydatid disease) in human immunodeficiency virus (HIV) infected patients in Spain: Report of two cases

There is little information on infections caused by larval cestodes in patients with human immunodeficiency virus (HIV) infection in developed countries. Two infections by larval cestodes were found in 714 HIV-infected patients studied from 1998 to 2004 at the Hospital General Universitario de Elche in Spain (Mediterranean Coast). The first patient was a Colombian immigrant diagnosed as having neurocysticercosis, and subsequently found to have HIV infection. The second case was an HIV-infected Spanish patient who developed hydatid disease of the liver, lung and peritoneum. Both patients died. Although infrequent, infections by larval cestodes constitute a cause of disease in HIV-infected patients in developed countries, and might be linked with a more severe presentation.

Liver transplantation in HIV-infected patients

Purpose of review The prognosis of infection caused by HIV has dramatically improved since the advent of highly active antiretroviral therapy. Thirty per cent of HIV-infected patients are co-infected with hepatitis C virus and 10% with hepatitis B virus, and a high number of HIV-infected patients will die as a result of viral hepatitis. There is current demand to offer liver transplantation to HIV-infected patients with life-threatening viral liver disease. Recent findings Transplantation in HIV/hepatitis B-infected patients gives excellent results using prophylaxis against hepatitis B virus reinfection with a combination of anti-hepatitis B surface immune globulins plus lamivudine/tenofovir. Survival in this group is over 85% at 2 years. In HIV/hepatitis C-infected patients the main problem is the reinfection of the graft by hepatitis C, which is more severe and more rapid than in monoinfected patients. In addition, hepatotoxicity caused by highly active antiretroviral therapy has been observed in this population. The survival in this group is 70% at 2 years posttransplantation. Summary Life-threatening liver disease in HIV-infected patients is now a validated indication. Results in HIV/hepatitis B-infected patients are excellent, but are less optimal in HIV/hepatitis C-co-infected patients. New antiviral strategies and anti-hepatitis C drugs will improve results in the future.

Cytomegalovirus-specific immunity and protection against viremia and disease in HIV-infected patients in the era of highly active antiretroviral therapy

To define the immune correlates of protection against cytomegalovirus (CMV) end-organ disease, CMV-specific interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) and CD8(+) and CD4(+) intracellular IFN-gamma synthesis assays were performed for subjects with CD4(+) cell counts of ≤50 cells/muL who were enrolled in a prospective observational study of CMV infection in the era of highly active antiretroviral therapy. Of 87 subjects, 46 developed viremia, 14 developed end-organ disease, and 20 died. Positive ELISPOT assay results, but not positive results for CD4(+) or CD8(+) intracellular IFN-gamma synthesis, were associated with delayed development of viremia and CMV end-organ disease or death. CMV viremia did not appear to boost CMV-specific immunity. ELISPOT assays may be used to identify HIV-infected patients who might benefit from anti-CMV prophylactic interventions.

Hepatic Steatosis Is Associated with Fibrosis, Nucleoside Analogue Use, and Hepatitis C Virus Genotype 3 Infection in HIV‐Seropositive Patients

We conducted a study to determine the prevalence and factors associated with hepatic steatosis in human immunodeficiency virus (HIV)-seropositive patients with hepatitis C and to investigate whether steatosis is associated with liver fibrosis. Retrospective chart reviews were conducted in 4 hospitals that serve community-based and incarcerated HIV-infected patients who had undergone a liver biopsy for evaluation of hepatitis C virus (HCV) infection during the period of 2000-2003. Demographic characteristics and medication and laboratory data were collected from the time of the biopsy. A pathologist blinded to all clinical data evaluated the specimens. The primary outcome was presence or absence of steatosis. Of 260 HIV-HCV-coinfected patients, 183 met inclusion criteria and had a biopsy specimen adequate for review. Steatosis was present in 69% of patients (graded as minimal in 31%, mild in 27%, moderate in 18%, and severe in 1%). Factors associated with steatosis included use of dideoxynucleoside analogues, such as didanosine and stavudine (odds ratio [OR], 4.63; 95% confidence interval [CI], 1.55-13.82). There was a trend toward presence of steatosis and use of other nucleoside analogues or infection with HCV genotype 3 (OR, 2.65 [95% CI, 0.95-7.41] and 3.38 [95% CI, 0.86-13.28], respectively). The presence of steatosis was associated with fibrosis (OR, 1.37; 95% CI, 1.03-1.81). In this multiracial population of HIV-HCV-coinfected patients, steatosis was prevalent and was associated with severity of liver fibrosis. Use of nucleoside analogues (particularly didanosine and stavudine) and HCV genotype 3 infection were associated with hepatic steatosis. The development of steatosis is multifactorial in nature and may play a contributory role in the progression of liver disease in HIV-infected patients.

The changing spectrum of pulmonary disease in patients with HIV infection on antiretroviral therapy

The pulmonary manifestations of HIV disease in 2005 can be divided into two sets of presentations. For patients who do not have access to care, and who are not taking antiretroviral or chemoprophylactic drugs, opportunistic infections and neoplasms continue to occur. Pulmonary disease caused by Streptococcus pneumoniae, Pneumocystis carinii (now known as Pneumocystis jiroveci pneumonia; PCP), Mycobacterium tuberculosis, lymphoma, and Kaposi’s sarcoma present much as they did in the 1980s. Management has improved in terms of new diagnostic, therapeutic, and preventive strategies, as reviewed in guidelines issued jointly by the National Institutes of Health, Centers for Disease Control and Prevention, and Infectious Disease Society of America (available online at http://www.aidsinfo.nih.gov).

Bacterial Disease in HIV-Infected Patients

Bacterial Disease in HIV-Infected Patients

Neurological disease in HIV-infected patients in the era of highly active antiretroviral treatment: a Brazilian experience

To study characteristics of neurological disorders in HIV/AIDS patients and their relationship to highly active antiretroviral treatment, a cross-sectional study was conducted in an infectious disease public hospital in Belo Horizonte, Brazil, between February 1999 and March 2000. Of the 417 patients enrolled, neurological disease was observed in 194 (46.5%) and a new AIDS-defining neurological event developed in 23.7% of individuals. Toxoplasmosis (42.3%), cryptococcosis meningitis (12.9%) and tuberculosis (10.8%) were the most common causes of neurological complications. The majority (79.3%) of patients were on highly active antiretroviral treatment and these individuals using HAART showed higher CD4 cell counts (p = 0.014) and presented stable neurological disease (p = 0.0001), although no difference was found with respect to the profile of neurological complications. The neurological diseases continue to be a frequent complication of HIV/AIDS and infections are still its main causes in Brazil, even in the highly active antiretroviral treatment era.

Parotid disease and human immunodeficiency virus infection in Zambia

Among the salivary glands the parotid is unusual in that it contains lymphoid tissue within its capsule. The focus of infection with human immunodeficiency virus (HIV) is the lymphatic system and this results in a specific HIV-related pathology in the parotid. This 2-year surgical audit of parotid disease in HIV-infected patients in Lusaka shows patients presenting with parotid lymphadenopathy, bilateral diffuse parotid enlargement and parotid lymphoepithelial cysts. Clinical presentation and management are discussed.

Cryptococcal disease and HIV infection

In the era of highly active antiretroviral therapy for the treatment of HIV infection, the dramatic reductions in mortality and morbidity associated with immune reconstitution have included a marked decline in the incidence of opportunistic infections. Cryptococcus neoformans is a yeast that causes predominantly neurological disease in immunocompromised individuals, in particular those with HIV infection. It continues to be an important diagnosis in developing areas and amongst late presenters in parts of the world with access to highly active antiretroviral therapy. This article reviews the epidemiology, clinical features and management of cryptococcal disease in HIV-infected patients, particularly focusing on the history of, current guidelines for and future developments in antifungal therapy.

Epidemiologic Changes in Bacteremic Pneumococcal Disease in Patients With Human Immunodeficiency Virus in the Era of Highly Active Antiretroviral Therapy

The use of highly active antiretroviral therapy (HAART) may change the incidence of, and the risk and prognostic factors for, invasive pneumococcal disease in patients with human immunodeficiency virus (HIV). We prospectively studied 142 episodes of pneumococcal bacteremia in 122 HIV-infected adults. Eighty-five episodes occurred in the pre-HAART era (1986-1996) and 57 in the HAART era (1997-2002). A case-control study was conducted to identify risk factors for pneumococcal bacteremia in the HAART era. The incidence of pneumococcal bacteremia dropped from 24.1 episodes per 1000 patient-years in the pre-HAART era to 8.2 episodes per 1000 patient-years in the HAART era (P = .01). Compared with patients in the pre-HAART era, patients in the HAART era had more associated comorbidity (42% vs 26%; P = .04), fewer recurrences of bacteremia (4% vs 15%; P = .04), and a higher 30-day mortality rate (26% vs 8%; P=.004). High antibiotic resistance rates were observed in both periods. By multivariate analysis, the major risk factors for pneumococcal bacteremia in the HAART era were associated comorbidity (adjusted odds ratio [OR], 3.36), alcohol abuse (adjusted OR, 5.28), prior hospitalization (adjusted OR, 3.38), current smoking (adjusted OR, 5.19), and CD4 cell count lower than 100 cells/muL (adjusted OR, 2.38); while use of HAART (adjusted OR, 0.37) and pneumococcal vaccine (adjusted OR, 0.39) were protective factors. The widespread use of HAART and pneumococcal vaccine may decrease the incidence of invasive pneumococcal disease in HIV-infected patients. Risk factors and prognosis of pneumococcal bacteremia in the HAART era are more similar to those reported in non-HIV-infected individuals.

Prevention of cryptococcosis in HIV‐infected patients with limited access to highly active antiretroviral therapy: evidence for primary azole prophylaxis

Despite advances in the treatment of HIV disease, the incidence and mortality of invasive cryptococcal disease remain significant. A matched, case-control study was performed to examine the impact of highly active antiretroviral therapy (HAART) and azole use on the incidence of invasive cryptococcal disease in HIV-infected patients. The study was performed at a metropolitan hospital with a large indigent population and an incidence of seven cases of cryptococcal disease per 1000 persons with AIDS. Bivariate analysis, matched on CD4 count, revealed that both HAART use [odds ratio (OR) 0.43; 95% confidence interval (CI) 0.23-0.99] and azole use (OR 0.14; 95% CI 0.06-0.34) had a protective effect. Conditional logistic regression stratified on CD4 lymphocyte count revealed a protective role for azole use (OR 0.15; 95% CI 0.06-0.40) but not for HAART use (OR 0.47; 95% CI 0.18-1.26). Of note, the prevalence of HAART use was low in both cases and controls, with only 12% of cases and 23% of controls on HAART. The results of this study support previous evidence that azole use prevents invasive cryptococcal disease. Although current guidelines for the prophylaxis of opportunistic infections do not suggest routine prophylaxis for cryptococcal infection, this issue should be reconsidered, especially in populations that have a low prevalence of HAART use.

Guidelines for the Management of Chronic Kidney Disease in HIV-Infected Patients: Recommendations of the HIV Medicine Association of the Infectious Diseases Society of America

Samir K. Gupta, Joseph A. Eustace, Jonathan A. Winston, Ivy I. Boydstun, Tejinder S. Ahuja, Rudolph A. Rodriguez, Karen T. Tashima, Michelle Roland, Nora Franceschini, Frank J. Palella, Jeffrey L. Lennox, Paul E. Klotman, Sharon A. Nachman, Stephen D. Hall, and Lynda A. Szczech Divisions of Infectious Diseases and Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis; Division of Nephrology, Johns Hopkins University, School of Medicine and Department of Epidemiology, Bloomberg School of Public Health, Baltimore, Maryland; Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, and Division of Nephrology and Hypertension and Division of Infectious Diseases, Department of Pediatrics, State University of New York, Stony Brook; Division of Nephrology, Department of Medicine, University of Texas Medical Branch, Galveston; Division of Nephrology, Department of Medicine, San Francisco General Hospital and Positive Health Program at San Francisco General Hospital and the UCSF AIDS Research Institute, Department of Medicine, University of California at San Francisco; Division of Infectious Diseases, Department of Medicine, The Miriam Hospital, Brown Medical School, Providence, Rhode Island; Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, and Duke Clinical Research Institute and the Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, North Carolina; Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and Grady Infectious Disease Program, Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia